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dc.contributor.authorGonzález-Sánchez, Ana
dc.contributor.authorJaraíz-Rodríguez, Myriam
dc.contributor.authorDomínguez Prieto, Marta
dc.contributor.authorHerrero González, Sandra
dc.contributor.authorMedina Jiménez, José María
dc.contributor.authorTabernero Urbieta, María Aránzazu 
dc.date.accessioned2020-02-04T07:42:40Z
dc.date.available2020-02-04T07:42:40Z
dc.date.issued2016
dc.identifier.citationGonzález-Sánchez, A., Jaraíz-Rodríguez, M., Domínguez-Prieto, M., Herrero-González, S., Medina, J. M., & Tabernero, A. (2016). Connexin43 recruits PTEN and Csk to inhibit c-Src activity in glioma cells and astrocytes. Oncotarget, 7(31), 49819.es_ES
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/10366/140763
dc.description.abstract[EN] Connexin43 (Cx43), the major protein forming gap junctions in astrocytes, is reduced in high-grade gliomas, where its ectopic expression exerts important effects, including the inhibition of the proto-oncogene tyrosine-protein kinase Src (c-Src). In this work we aimed to investigate the mechanism responsible for this effect. The inhibition of c-Src requires phosphorylation at tyrosine 527 mediated by C-terminal Src kinase (Csk) and dephosphorylation at tyrosine 416 mediated by phosphatases, such as phosphatase and tensin homolog (PTEN). Our results showed that the antiproliferative effect of Cx43 is reduced when Csk and PTEN are silenced in glioma cells, suggesting the involvement of both enzymes. Confocal microscopy and immunoprecipitation assays confirmed that Cx43, in addition to c-Src, binds to PTEN and Csk in glioma cells transfected with Cx43 and in astrocytes. Pull-down assays showed that region 266–283 in Cx43 is sufficient to recruit c-Src, PTEN and Csk and to inhibit the oncogenic activity of c-Src. As a result of c-Src inhibition, PTEN was increased with subsequent inactivation of Akt and reduction of proliferation of human glioblastoma stem cells. We conclude that the recruitment of Csk and PTEN to the region between residues 266 and 283 within the C-terminus of Cx43 leads to c-Src inhibition.es_ES
dc.format.mimetypeapplicatio/pdf
dc.language.isoenges_ES
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectConnexines_ES
dc.subjectSrces_ES
dc.subjectGliaes_ES
dc.subjectCNSes_ES
dc.subjectGap junctionses_ES
dc.subject.meshCells*
dc.subject.meshGap Junctions*
dc.titleConnexin43 recruits PTEN and Csk to inhibit c-Src activity in glioma cells and astrocyteses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.relation.publishversionhttps://doi.org/10.18632/oncotarget.10454
dc.subject.unesco2302 Bioquímicaes_ES
dc.subject.unesco2490 Neurocienciases_ES
dc.identifier.doi10.18632/oncotarget.10454
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.identifier.essn1949-2553
dc.journal.titleOncotargetes_ES
dc.volume.number7es_ES
dc.issue.number31es_ES
dc.page.initial49819es_ES
dc.page.final49833es_ES
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones_ES
dc.subject.decscélulas*
dc.subject.decsuniones comunicantes*


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivatives 4.0 Internacional